Tithonia diversifolia (Hemsl.) extract attenuates cognitive dysfunction, oxidative stress and neuroinflammation in a model of sporadic Alzheimer’s disease induced by streptozotocin

Abstract

Aim: Alzheimer’s disease (AD) is a chronic neurodegenerative brain dysfunction and the most common form of dementia, especially in the elderly, and is considered a serious problem for health systems worldwide. It is a multifactorial and progressive condition, characterized by memory loss, personality changes and decline in cognitive function, in addition to neuropsychiatric complications such as depression, anxiety, sleep disorders, and others, further reducing the quality of life of patients with AD. Since the introduction of galantamine in AD therapy, medicinal plants and herbal remedies are gaining increasing interest as complementary and alternative interventions and are a valuable source for the development of drug candidates for AD. This work aims to explore Tithonia diversifolia ethanol extract (EETD), which showed an acetylcholinesterase (AChE) inhibitory activity like rivastigmine, as a new candidate for molecular targets of AD.

Methods: Mice were submitted to intracerebroventricular (I.C.V.) streptozotocin (STZ)-induced AD (2.5 mg/mL) and separated into different groups: sham, vehicle, rivastigmine (0.6 mg/kg), and EETD (0.1, 1.0, and 3.0 mg/kg). After AD induction, the animals were treated for 24 days and submitted to behavioral tests of memory, anxiety and depression. After the tests, the animals were sacrificed and the hippocampus was removed for assays of oxidative stress, AChE activity and markers of neuroinflammation. In vitro studies evaluated the effect of the extract on tau hyperphosphorylation, beta-amyloid (Aβ), and nitric oxide (NO) production.

Results: EETD promoted a reduction in STZ-induced behavioral parameters of depression and anxiety, as well as reversed memory deficits. Biochemical assays revealed that EETD increased antioxidant defenses, as well as decreased levels of neuroinflammation markers. In addition, EETD partially inhibited Aβ production.

Conclusions: The results together suggest that the plant exhibits therapeutic relevance in AD. However, studies are needed to identify the phytoconstituents responsible for such effects.

Keywords

Tithonia diversifolia / Alzheimer’s / streptozotocin / oxidative stress / neuroinflammation

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